Continuing Education Activity

Bariatric surgery has been reported to help achieve more significant and sustained weight loss than non-surgical management in patients with severe obesity. The number of bariatric surgeries performed has increased yearly from 2011 through 2019. Post-bariatric surgery hypoglycemia is an increasingly recognized complication. It can have significant effects on the quality of life of an individual. This activity reviews the various patterns of post-bariatric surgery hypoglycemia, pathophysiology, evaluation, differential diagnosis, and treatment and highlights the role of the interprofessional team in evaluating and treating patients with this condition.

Objectives:

• Describe the pathophysiology of post-bariatric surgery hypoglycemia.
• Identify the typical presentation of a patient with post-bariatric surgery hypoglycemia.
• Implement recommended diagnostic evaluation criteria for differentiating etiologies of hypoglycemia
• Apply best practices in the treatment of post-bariatric surgery hypoglycemia including medical nutrition therapy, pharmacotherapy, and surgical management.

Introduction

Obesity is a common, chronic, and often relapsing disease characterized by excess adipose tissue accumulation. The World Health Organization (WHO) considers a body mass index (BMI) ≥30 kg/m as obese and defines severe obesity as a BMI of 40 or higher (also classified as Class 3 obesity). 

According to the National Nutritional Health and Examination Survey (NHANES) data (2017 to 2020), the prevalence of obesity among children and adolescents aged 2 to 19 years is 19.7%; among adults aged 20 and over, the age-adjusted prevalence of obesity is 41.9%, and the prevalence of severe obesity is 9.2%. Obesity increases the risk of other medical conditions such as diabetes mellitus type 2, fatty liver disease, hypertension, coronary artery disease, stroke, dementia, obstructive sleep apnea, osteoarthritis, dysthymia, etc.[1] According to the Centers for Disease Control and Prevention (CDC), the estimated annual obesity-related medical care cost was approximately $173 billion in 2019. 

Bariatric surgery has been reported to help achieve more significant and sustained weight loss than non-surgical management in patients with severe obesity.[2] According to data from the American Society for Metabolic and Bariatric Surgery (ASMBS), the number of bariatric surgeries performed has increased yearly from 2011 through 2019.[3] Hence, it is essential to be aware of post-surgery adverse events.

Post-bariatric surgery hypoglycemia is an increasingly recognized complication. It has been referred to as late dumping syndrome, reactive hypoglycemia, or postprandial hyper-insulinemic hypoglycemia. However, there is no specific definition of post-bariatric surgery hypoglycemia. It has been thought of as a condition characterized by symptoms of hypoglycemia occurring after a meal in individuals who have undergone weight loss surgery. However, with more sensitive methods, such as continuous glucose monitoring (CGM), other patterns of hypoglycemia are being identified. Post-bariatric surgery hypoglycemia is commonly associated with Roux-en-Y gastric bypass (RYGB) surgery. However, it can also occur with different types of bariatric surgeries, such as sleeve gastrectomy (SG) and laparoscopically adjustable gastric band (LAGB).[3]

Etiology

The etiology is suspected to be related to altered anatomy post-surgery, its effects on the transition time of ingested food, and hormonal and glycemic patterns. The effects are usually compounded by consuming large meals of simple sugars and refined fats.[3]

Impairment of fasting glucose regulation has also been recently recognized, although the underlying mechanisms are yet to be understood.[4]

Epidemiology

Reported risk factors for hypoglycemic complications following bariatric surgery include female sex, Roux-en-Y gastric bypass (RYGB) surgery history, longer time since surgery, and absence of preexisting diabetes.[5][6] However, it's worth noting that approximately 70% to 80% of individuals undergoing bariatric surgery are female.[7]

A randomized controlled trial found no significant difference in the occurrence of hypoglycemia after SG compared with RYGB, but RYGB may be associated with more severe episodes.[8] In a study using continuous glucose monitoring, Nocturnal and asymptomatic hypoglycemia has been reported to occur more frequently after Sleeve Gastrectomy (SG) than RYGB, whereas RYGB is associated more often with post-prandial and symptomatic hypoglycemic events.[4]

There is wide variation in the reported prevalence of hypoglycemia post-bariatric surgery. This variation is likely due to different study methodologies, variability in testing, and definitions of hypoglycemia used. However, with increasing recognition of conditions such as asymptomatic hypoglycemia, meal-independent hypoglycemia, and the use of more sensitive methods such as CGM, it has become apparent that the condition is underreported. 

Studies that have relied on patient recall of symptoms have noted a prevalence of post-prandial symptomatic hypoglycemia ranging from 0.1 to 34%.[3] A prospective study that used Oral Glucose Tolerance Test (OGTT) reported a prevalence of 25.6%.[9]  Smaller studies using more sensitive methods, such as CGM, reported hypoglycemic episodes in as many as 55 to 75% of the patients studied.[4][10] 

The actual burden of this condition and risk factors are yet to be determined and would require extensive studies.

Pathophysiology

The pathophysiology still needs to be fully elucidated. There are likely different mechanisms underlying different patterns of hypoglycemia. 

Postprandial hypoglycemia is thought to occur in two phases:

1. Induction of post-meal hyper-insulinemia
2. Maintenance of inappropriately high levels of insulin

Post-Meal Hyperinsulinemia

In individuals with post-RYGB hypoglycemia, ingested food induces faster, higher glycemic peaks and lower nadirs.[11] 

Glucagon-like peptide -1 (GLP -1) is secreted by the intestinal L cells in response to ingested food, and it contributes to insulin secretion in a dose-dependent (glucose-dependent) manner. In individuals with post-bariatric surgery hypoglycemia, it was noted that meal-induced GLP-1 levels are elevated and likely result in an exaggerated insulin response compared to those without symptoms of hypoglycemia.[3]

Ghrelin suppresses insulin secretion and opposes its action. Its secretion is decreased after gastric bypass surgery, which can contribute to hypoglycemia.[12][13] Non-hormonal gut factors may also contribute to meal-induced hyper-insulinemia.[14]

Maintenance of Inappropriately High Levels of Insulin 

Specific mechanisms perpetuate high insulin levels in individuals with post-RYGB hypoglycemia, even after developing hypoglycemia. They have lower beta cell suppression in response to low blood sugar levels. They also may have diminished insulin clearance. Increased insulin sensitivity after weight loss and disturbed counter-regulatory hormonal responses to hypoglycemia also have a role.[3]

The effects of other insulinotropic factors and changes in insulin sensitivity may be contributory, although they still need to be fully understood. Increased beta cell mass was previously implicated; however, it is currently not considered a significant cause of hypoglycemia.[3] The mechanisms for meal-independent hypoglycemia are even less known.[4]

Histopathology

No consistent histopathologic pattern has been found. Initial reports of β-cell hypertrophy and islet cell hyperplasia were seen in the pancreas tissue samples from patients who underwent partial pancreatectomy to manage postprandial hypoglycemia after bariatric surgery.[15] However, these findings have been disputed. Other studies have reported the presence of increased beta cell nuclear diameter in patients who experience post-bariatric surgery hypoglycemia.[16]

History and Physical

Patients with late dumping syndrome can present autonomic or neuroglycopenic hypoglycemia symptoms months to years after the surgery, usually 1 to 3 hours after a meal. The consumption of large meals rich in simple carbohydrates exacerbates symptoms.[3]

The autonomic symptoms can be anxiety, sweating, tremors, and palpitations. Neuroglycopenic symptoms include confusion, fatigue, light-headedness, slurred speech, blurred vision, and disorientation. Seizures or a coma may occur in severe cases.[17]

Postprandial hypoglycemia is seen more commonly after RYGB, whereas meal-independent hypoglycemia occurs more commonly after Sleeve Gastrectomy.[4] However, postprandial hypoglycemia can also be seen after SG and LAGB, and some patients can have a mixed pattern. 

Some individuals with repeated episodes of hypoglycemia may develop hypoglycemia unawareness defined as the development of symptoms of neuroglycopenia before the onset of autonomic warning symptoms.[18]

There are no physical exam findings specific to this condition.

Evaluation

A consensus on the criteria for diagnosing postprandial hyperinsulinemic hypoglycemia after bariatric surgery is yet to be developed. Making a diagnosis can be challenging due to the variation in symptoms and the definitions of hypoglycemia.

The International Hypoglycemia Study Group considers a glucose level of <3.0 mmol/L (<54 mg/dL) to indicate clinically significant hypoglycemia.[19]

The ASMBS recommends the following criteria for diagnosis of postprandial hyperinsulinemic hypoglycemia or late dumping syndrome:[3]

1. Symptoms occurring more than one year after surgery
2. Normal fasting glucose and insulin levels
3. Correlation of symptoms with hypoglycemia, followed by spontaneous resolution of hypoglycemia
4. Positive provocative test.

Others have recommended additional criteria and specific cut-off values - the presence of hyperinsulinemia (serum insulin >50 µU/L or 300 pmol/L) concurrently with hypoglycemia (plasma glucose <50 mg/dL or 2.8 mmol/L) after a mixed meal.[20]

Provocative tests such as the oral glucose tolerance test (OGTT) and mixed meal tolerance test (MMTT) aid in the diagnosis. OGTT involves the administration of 75 to 100 grams of glucose followed by serial serum glucose measurements at intervals up to 120 to 240 minutes after administration. In MMTT, a standardized meal of carbohydrates, protein, and fat is administered. Glucose and insulin levels are determined during fasting and 30-minute intervals after the mixed meal.[3] 

In patients with bariatric surgery, an oral glucose tolerance test (OGTT) for evaluation of meal-induced hypoglycemia may not be well tolerated since hyperosmolar glucose liquid loads may provoke severe hypoglycemia and should be avoided. A mixed meal test with carbohydrates, protein, and fat may be better, but this approach remains controversial. Any provoked tests should be performed in a supervised setting with trained medical personnel equipped to deal with the situation due to the risk of a severe hypoglycemic event.[11]

Continuous glucose monitoring (CGM) is more sensitive and specific than provocative tests.[21] CGM provides more details regarding glucose excursions while allowing subjects to follow their usual feeding patterns. CGM has the added benefit of capturing asymptomatic hypoglycemia and fasting hypoglycemia episodes.

In individuals with fasting hypoglycemia, the possibility of insulinoma should be considered. Workup for insulinoma entails a 72-hour fasting test and computerized tomography (CT)/magnetic resonance imaging (MRI). Invasive studies such as endoscopic ultrasound or selective arterial calcium stimulation testing may be considered if the imaging is unrevealing.[3]

As the name implies, a 72-hour fasting test entails fasting for 72 hours (calorie-free beverages are allowed). Capillary blood samples for glucose are collected every 2 hours, and venous blood sugar samples are collected every 6 hours. Once blood sugar levels are less than 60 mg/dL, insulin, C-peptide, pro-insulin, and beta-hydroxybutyrate should also be collected.[22] Concurrently with hypoglycemia, a high insulin level, high C-peptide levels, and absence of sulfonylurea suggest insulinoma.[23]

Some clinicians consider the presence of Whipple’s triad (Measured low blood glucose with corresponding symptoms of hypoglycemia and low blood glucose and the relief of symptoms when low blood glucose is corrected) essential for diagnosis. However, since some people can have atypical symptoms of hypoglycemia or asymptomatic hypoglycemia, reliance on Whipple’s triad may miss the diagnosis in these individuals. Hence, a clinician needs to be aware of the various patterns of hypoglycemia, as this may inform the choice of diagnostic tests ordered. 

It is also crucial to consider other conditions, such as insulinoma, adrenal insufficiency, liver dysfunction, and medication-induced hypoglycemia, and rule them out when indicated based on history and physical examination.

Diagnostic evaluation for differentiating etiologies of hypoglycemia is summarized in Table 1. 

Table

Table 1.

Treatment / Management

Medical Nutrition Therapy

Medical nutritional therapy is the first line of treatment. A strategy of consuming small portions of low glycemic index carbohydrates (30 grams of carbohydrates per meal, 15 grams per snack), adequate protein consumption (30 grams per meal and total of 60 to 80 grams/day), adequate fat consumption (15 grams/meal, 5 grams/snack), spacing meals 3 to 4 hours apart, avoidance of alcohol, caffeine, and fluids with meals is recommended. 

Avoiding high glycemic index foods is essential because a sudden rise in glucose can trigger more insulin release after meals and contribute to significant post-prandial hypoglycemia. High glycemic foods are digested quickly, whereas low glycemic foods are digested relatively slowly and cause a relatively slow rise in glucose levels.[24]

Pharmacotherapy

Pharmacotherapy may be considered for individuals with moderate-severe symptoms refractory to nutritional therapy; however, large-scale studies comparing the efficacy of medications are yet to be performed. The choice in the use of medications depends on the clinician's preference/experience and patient choice. The use of nifedipine, acarbose, GLP-1 analogs, diazoxide, and somatostatin analogs for treatment has been reported in case reports and small case series.  

Acarbose, an alpha-glucosidase inhibitor, delays the digestion of carbohydrates and may help decrease post-prandial glucose level spikes. Diazoxide acts via ATP-sensitive Potassium channels to inhibit the secretion of insulin. Somatostatin analogs slow gastric and small bowel transit of ingested material, affecting the release of hormones, insulin, and vasculature tone. Calcium channel blockers work via calcium channels on Beta cells to affect insulin secretion.[25][26]

The International consensus on diagnosing and managing dumping syndrome endorses using acarbose as the first-line pharmacotherapeutic agent and using somatostatin analogs in patients not responding to acarbose. Usually, acarbose at a dose of 50–100 mg three times daily, with meals recommended. The adverse effects associated with acarbose are bloating and flatulence. Somatostatin analogs require frequent injections.[25] Some clinicians have used combination therapy.

A recent randomized, placebo-controlled crossover study (PREVENT) reported promising results with Avexitide, a GLP -1 antagonist, in treating post-bariatric surgery hypoglycemia.[27] The "DEEP-EMPA" trial investigates the effects of Empagliflozin, a sodium-glucose cotransporter 2-inhibitor, on hypoglycemia post-bariatric surgery.[28]

Surgical Management

Surgical management may be considered for patients with moderate-to-severe symptoms refractory to nutritional therapy and pharmacotherapy. As with pharmacotherapy, large-scale trials comparing efficacy and safety are yet to be performed; surgical modality depends on the clinician's preference/expertise, comorbidities, anatomy, and patient choice. Gastrostomy tube placement in the remnant stomach, gastric outlet restriction surgery, RYGB reversal, and conversion of RYGB to SG have been reported in small case series. A partial pancreatectomy has been performed for this indication. However, it has not been found effective, and the ASMBS does not recommend it.[3]

Differential Diagnosis

An insulinoma should be considered in the differential diagnosis and ruled out. Postprandial hypoglycemia has been seen in individuals with nonalcoholic fatty liver disease (NAFLD); obesity is a risk factor for developing NAFLD.[29]

Exogenous insulin or secretagogue use may also induce hypoglycemia; C peptide levels (low in case of exogenous insulin, normal or elevated with secretagogues) and medication screening may help investigate these causes.

In the appropriate context, the differential diagnosis may also consider hormone deficiencies, autoimmune conditions, or non-islet cell tumors.[11]

Prognosis

Patients with mild to moderate symptoms usually respond well to nutritional therapy.[3] However, only limited data are available regarding the proportion of people with post-bariatric surgery hypoglycemia requiring pharmacotherapy, with pharmacotherapy failure requiring surgery for correction and failure of surgery to correct this condition. 

A recent retrospective observational study of patients with post-bariatric surgery hypoglycemia reported on outcomes of patients who had failed nutritional therapy. It defined the efficacy of medication as “greater than fifty percent reduction of hypoglycemic symptoms and as a combination of no or almost no hypoglycemic events.” In this study, overall reported medication efficacy ranged from 45 to 80%. Approximately 20% of the patients were referred for surgical treatment due to the failure of conservative measures. About 63% of the patients who underwent surgery reported complete resolution of the symptoms, about 16% reported 50 to 100% resolution of the symptoms, and no improvement was reported in 21%. Different types of surgeries had different efficacies.[30] However, more studies are needed to draw firm conclusions. Persistent symptoms can have profound effects on quality of life.

Complications

Severe hypoglycemia can be associated with signs and symptoms such as anxiety, irritability, slurred speech, shakiness, disorientation, agitation, seizures, loss of consciousness, and even death. 

Repeated episodes of hypoglycemia can result in a condition called “hypoglycemia unawareness,” wherein despite low blood sugar levels, the counter-regulatory responses are blunted, and the symptoms of hypoglycemia diminish over time. A study in patients with post-bariatric surgery hypoglycemia demonstrated impaired driving performance associated with low glucose levels even in the absence of symptoms of hypoglycemia.[30]

In patients with diabetes mellitus, hypoglycemia can also have insidious harmful effects on various organ systems, significantly affecting the quality of life. However, the long-term effects of post-bariatric surgery hypoglycemia are unknown.[31]

Deterrence and Patient Education

The risk factors for developing post-bariatric surgery hypoglycemia are not entirely understood; hence, more data is needed to inform patient selection to avoid this condition. Individuals considering bariatric surgery for weight loss should be aware of the symptoms of post-bariatric surgery hypoglycemia, its effects on quality of life, and the treatment options. 

Avoiding large meals with simple carbohydrates and consuming small, frequent meals rich in protein, healthy fats, and fiber may help improve symptoms. Pharmacotherapy can be considered for people who do not respond to dietary changes. Patients who fail conservative measures may need surgical interventions to treat this condition.

Pearls and Other Issues

Post-bariatric surgery hypoglycemia is usually a late complication of weight loss surgeries. It has been thought of as post-prandial hypoglycemia; however, meal-independent hypoglycemia is also recognized. It can present with symptoms of hypoglycemia; however, in some cases, hypoglycemia can be asymptomatic and still affect cognition. Treatment options include nutritional therapy, pharmacotherapy, and surgery.

Enhancing Healthcare Team Outcomes

Clinicians should be aware of this complication and discuss the possibility during pre-surgery counseling. Patients should meet with a clinical nutritionist before the procedure and determine whether the dietary changes required pre and post-procedure are feasible.

If a patient develops this complication, an interprofessional team comprising primary care providers, surgeons, endocrinologists, nutritionists, and pharmacists may help develop strategies to manage this condition. More data is needed to establish specific standards for multidisciplinary evaluation. The primary treatment is dietary modification; pharmacotherapy may be added if symptoms persist. In patients who have failed conservative measures, surgical therapies may be considered. The recommendations for treating post-bariatric surgery hypoglycemia are based on case series and expert opinion. [Level 5]

Review Questions

• Access free multiple choice questions on this topic.
• Click here for a simplified version.
• Comment on this article.

References

1.

Blüher M. Obesity: global epidemiology and pathogenesis. Nat Rev Endocrinol. 2019 May;15(5):288-298. [PubMed: 30814686]

2.

Dietz WH, Baur LA, Hall K, Puhl RM, Taveras EM, Uauy R, Kopelman P. Management of obesity: improvement of health-care training and systems for prevention and care. Lancet. 2015 Jun 20;385(9986):2521-33. [PubMed: 25703112]

3.

Eisenberg D, Azagury DE, Ghiassi S, Grover BT, Kim JJ. ASMBS Position Statement on Postprandial Hyperinsulinemic Hypoglycemia after Bariatric Surgery. Surg Obes Relat Dis. 2017 Mar;13(3):371-378. [PubMed: 28110984]

4.

Lupoli R, Lembo E, Ciciola P, Schiavo L, Pilone V, Capaldo B. Continuous glucose monitoring in subjects undergoing bariatric surgery: Diurnal and nocturnal glycemic patterns. Nutr Metab Cardiovasc Dis. 2020 Oct 30;30(11):1954-1960. [PubMed: 32807631]

5.

Lee CJ, Clark JM, Schweitzer M, Magnuson T, Steele K, Koerner O, Brown TT. Prevalence of and risk factors for hypoglycemic symptoms after gastric bypass and sleeve gastrectomy. Obesity (Silver Spring). 2015 May;23(5):1079-84. [PMC free article: PMC4414701] [PubMed: 25866150]

6.

Lee CJ, Brown TT, Schweitzer M, Magnuson T, Clark JM. The incidence and risk factors associated with developing symptoms of hypoglycemia after bariatric surgery. Surg Obes Relat Dis. 2018 Jun;14(6):797-802. [PubMed: 29678347]

7.

Poelemeijer YQM, Liem RSL, Våge V, Mala T, Sundbom M, Ottosson J, Nienhuijs SW. Perioperative Outcomes of Primary Bariatric Surgery in North-Western Europe: a Pooled Multinational Registry Analysis. Obes Surg. 2018 Dec;28(12):3916-3922. [PMC free article: PMC6223749] [PubMed: 30027332]

8.

Capristo E, Panunzi S, De Gaetano A, Spuntarelli V, Bellantone R, Giustacchini P, Birkenfeld AL, Amiel S, Bornstein SR, Raffaelli M, Mingrone G. Incidence of Hypoglycemia After Gastric Bypass vs Sleeve Gastrectomy: A Randomized Trial. J Clin Endocrinol Metab. 2018 Jun 01;103(6):2136-2146. [PubMed: 29590421]

9.

Brix JM, Kopp HP, Höllerl F, Schernthaner GH, Ludvik B, Schernthaner G. Frequency of Hypoglycaemia after Different Bariatric Surgical Procedures. Obes Facts. 2019;12(4):397-406. [PMC free article: PMC6758723] [PubMed: 31234171]

10.

Kefurt R, Langer FB, Schindler K, Shakeri-Leidenmühler S, Ludvik B, Prager G. Hypoglycemia after Roux-En-Y gastric bypass: detection rates of continuous glucose monitoring (CGM) versus mixed meal test. Surg Obes Relat Dis. 2015 May-Jun;11(3):564-9. [PubMed: 25737101]

11.

Salehi M, Vella A, McLaughlin T, Patti ME. Hypoglycemia After Gastric Bypass Surgery: Current Concepts and Controversies. J Clin Endocrinol Metab. 2018 Aug 01;103(8):2815-2826. [PMC free article: PMC6692713] [PubMed: 30101281]

12.

Cummings DE, Foster-Schubert KE, Overduin J. Ghrelin and energy balance: focus on current controversies. Curr Drug Targets. 2005 Mar;6(2):153-69. [PubMed: 15777186]

13.

Sethi P, Thillai M, Nain PS, Ahuja A, Aulakh N, Khurana P. Role of Hunger Hormone "Ghrelin" in Long-Term Weight Loss Following Laparoscopic Sleeve Gastrectomy. Niger J Surg. 2018 Jul-Dec;24(2):121-124. [PMC free article: PMC6158981] [PubMed: 30283224]

14.

Honka H, Salehi M. Postprandial hypoglycemia after gastric bypass surgery: from pathogenesis to diagnosis and treatment. Curr Opin Clin Nutr Metab Care. 2019 Jul;22(4):295-302. [PMC free article: PMC6598692] [PubMed: 31082828]

15.

Service GJ, Thompson GB, Service FJ, Andrews JC, Collazo-Clavell ML, Lloyd RV. Hyperinsulinemic hypoglycemia with nesidioblastosis after gastric-bypass surgery. N Engl J Med. 2005 Jul 21;353(3):249-54. [PubMed: 16034010]

16.

Meier JJ, Butler AE, Galasso R, Butler PC. Hyperinsulinemic hypoglycemia after gastric bypass surgery is not accompanied by islet hyperplasia or increased beta-cell turnover. Diabetes Care. 2006 Jul;29(7):1554-9. [PubMed: 16801578]

17.

Cryer PE. Symptoms of hypoglycemia, thresholds for their occurrence, and hypoglycemia unawareness. Endocrinol Metab Clin North Am. 1999 Sep;28(3):495-500, v-vi. [PubMed: 10500927]

18.

Szadkowska A, Czyżewska K, Pietrzak I, Mianowska B, Jarosz-Chobot P, Myśliwiec M. Hypoglycaemia unawareness in patients with type 1 diabetes. Pediatr Endocrinol Diabetes Metab. 2018;2018(3):126-134. [PubMed: 30786677]

19.

International Hypoglycaemia Study Group. Glucose Concentrations of Less Than 3.0 mmol/L (54 mg/dL) Should Be Reported in Clinical Trials: A Joint Position Statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care. 2017 Jan;40(1):155-157. [PubMed: 27872155]

20.

Bantle JP, Ikramuddin S, Kellogg TA, Buchwald H. Hyperinsulinemic hypoglycemia developing late after gastric bypass. Obes Surg. 2007 May;17(5):592-4. [PubMed: 17658016]

21.

Halperin F, Patti ME, Skow M, Bajwa M, Goldfine AB. Continuous glucose monitoring for evaluation of glycemic excursions after gastric bypass. J Obes. 2011;2011:869536. [PMC free article: PMC3038694] [PubMed: 21331295]

22.

Prieto-Saldarriaga C, Builes-Montaño CE, Arango-Toro CM, Manotas-Echeverry C, Pérez-Cadavid JC, Álvarez-Payares JC, Rodríguez-Arrieta LA. Insulinoma-related Endogenous Hypoglycaemia with a Negative Fasting Test: A Case Report and Literature Review. Eur J Case Rep Intern Med. 2022;9(9):003484. [PMC free article: PMC9586516] [PubMed: 36299851]

23.

Okabayashi T, Shima Y, Sumiyoshi T, Kozuki A, Ito S, Ogawa Y, Kobayashi M, Hanazaki K. Diagnosis and management of insulinoma. World J Gastroenterol. 2013 Feb 14;19(6):829-37. [PMC free article: PMC3574879] [PubMed: 23430217]

24.

Suhl E, Anderson-Haynes SE, Mulla C, Patti ME. Medical nutrition therapy for post-bariatric hypoglycemia: practical insights. Surg Obes Relat Dis. 2017 May;13(5):888-896. [PMC free article: PMC5469688] [PubMed: 28392017]

25.

Scarpellini E, Arts J, Karamanolis G, Laurenius A, Siquini W, Suzuki H, Ukleja A, Van Beek A, Vanuytsel T, Bor S, Ceppa E, Di Lorenzo C, Emous M, Hammer H, Hellström P, Laville M, Lundell L, Masclee A, Ritz P, Tack J. International consensus on the diagnosis and management of dumping syndrome. Nat Rev Endocrinol. 2020 Aug;16(8):448-466. [PMC free article: PMC7351708] [PubMed: 32457534]

26.

Ames A, Lago-Hernandez CA, Grunvald E. Hypoglycemia After Gastric Bypass Successfully Treated With Calcium Channel Blockers: Two Case Reports. J Endocr Soc. 2019 Jul 01;3(7):1417-1422. [PMC free article: PMC6608552] [PubMed: 31286108]

27.

Craig CM, Lawler HM, Lee CJE, Tan M, Davis DB, Tong J, Glodowski M, Rogowitz E, Karaman R, McLaughlin TL, Porter L. PREVENT: A Randomized, Placebo-controlled Crossover Trial of Avexitide for Treatment of Postbariatric Hypoglycemia. J Clin Endocrinol Metab. 2021 Jul 13;106(8):e3235-e3248. [PMC free article: PMC8277203] [PubMed: 33616643]

28.

Ferreira A, Emara AFA, Herzig D, Melmer A, Vogt AP, Nakas CT, Facchinetti A, Dalla Man C, Bally L. Study protocol for a randomised, double-blind, placebo-controlled crossover trial assessing the impact of the SGLT2 inhibitor empagliflozin on postprandial hypoglycaemia after gastric bypass. BMJ Open. 2022 Sep 19;12(9):e060668. [PMC free article: PMC9486284] [PubMed: 36123073]

29.

Oki Y, Ono M, Hyogo H, Ochi T, Munekage K, Nozaki Y, Hirose A, Masuda K, Mizuta H, Okamoto N, Saibara T. Evaluation of postprandial hypoglycemia in patients with nonalcoholic fatty liver disease by oral glucose tolerance testing and continuous glucose monitoring. Eur J Gastroenterol Hepatol. 2018 Jul;30(7):797-805. [PMC free article: PMC5999378] [PubMed: 29634665]

30.

de Heide LJM, Wouda SHT, Peters VJT, Oosterwerff-Suiker M, Gerdes VA, Emous M, van Beek AP. Medical and surgical treatment of postbariatric hypoglycaemia: Retrospective data from daily practice. Diabetes Obes Metab. 2023 Mar;25(3):735-747. [PubMed: 36377811]

31.

Kalra S, Mukherjee JJ, Venkataraman S, Bantwal G, Shaikh S, Saboo B, Das AK, Ramachandran A. Hypoglycemia: The neglected complication. Indian J Endocrinol Metab. 2013 Sep;17(5):819-34. [PMC free article: PMC3784865] [PubMed: 24083163]

Disclosure: Anand Athavale declares no relevant financial relationships with ineligible companies.

Disclosure: Venu Madhav Ganipisetti declares no relevant financial relationships with ineligible companies.